N-acixphenothiazines



Patented Feb. 8, 1949 7 2,461,460

UNITED STATES PATENT OFFICE N ACYLPHEN DTHIAZIN ES Philip S. Winnek and Herman Eldridge Faith,

Indianapolis, Ind, assignors to Allied Laboratories, Inc., Kansas City, Mo., a corporation of Delaware No Drawing. Application December 22, 1945, Serial No. 637,121

4 Claims. (Cl. 260-243) 1 2 The present invention relates to the new chemithus formed was crystallized from '75 ethyl alcal compounds, N-acylphencthiazines. More parcoho], with charcoal being used to decolorize it. ticularly, this invention relates to the preparation The product melted at 179 to 181 C. of N-carboxyacylphenothiazines wherein the car- The product produced in accordance with the boxyacyl group is derived from a dicarboxylic above example has the following formula:

acid. S

Our new compounds may be represented by the following formula:

O=CCH2CH2COOH \N/ CM iaOsNS (299.33)

and the analysis shows it to be the desired compound wherein R represents a carboxyacyl radical derived from a dicarboxylic acid. C H

Phenothiazine is very widely used as an anthelmintic and especially in the veterinary field. percent 64.196 ms While phenothiazine is an outstanding anthel- Found 64.19 4.14 mintic, it has some properties which make it dif- 2O 5 ficult to formulate into pharmaceutical preparations and to administer to domestic animals. For valilous other CamPXYaYlphemthmmes mclud" example, phenothiazine is extremely diflicult to ed present Y -m obtained, by wet with Wat er and in most cases when mixtures substituting other dicarboxylic acid anhydrides with water are to be employed it is necessary to or dicarboxylic acid chlorides for the succinic use substances such as bentonite and/or wetting g ankllydnde of the above example caragents to facilitate the preparation of the aqueous oxyacy group thgrefore. be dam/ed j mixture. The products of our invention produce any dlcarmxifhc an anthelmmtic effect Very Similar to if not glutaric, ad1p1c,pime11c ,s uberic, azelaic, sebacic, identical with that of phenothiazine. They pos- P F pi t maleic' citmmic sess the additional advantage that the presence ghthahc fi i i dlmthybphthahc and of the free carboxy group renders them either roxy'me y hallo acld' water soluble or miscible with slightly alkaline The abqve descxtlptlon and example a f solutions and hence they are more easily incored F luustratlve 1 Any modlficatmn porated into preparations for administration to t t whlch to the 9 of the invention is intended to be included With- We do not desire to limit our present invenm the scope of P tion to any particular method for the production What We claim of our compounds. We have found, however, that The compound of the formula they may be readily obtained by reacting phenothiazine with anhydrides of dicarboxylic acids.

In many cases, the reaction can be carried out by direct heating of a mixture of phenothiazine with the anhydride of the dicarboxylic acid. In

other cases, it may be desirable to carry the re- O= JJOH2CHNOOH action out by heating the reactants in an inert The Process Pmducing organic Solvent. phenothiazines which comprises reacting pheno- The following examples will serve to illustrate thiazine with dicarboxylic acid anhydride- 2. method for the production of one of our pre- 3. he process fo pr u -succ y p enoferred n-carboxyacylphenothiazines. thiazine which comprises reacting phenothiazine with succinic acid anhydride. Pwpamtmn of N'succmylphenothmzme 4. The process for producing n-succinylpheno- Fifteen parts of phenothiazine and thirty parts thiazine which comprises reacting phenothiazine of succinic anhydride were mixed and heated with with succinic acid anhydride by heating said rean oil bath at 150 C. for 16 hours. The fused actants at a temperature of about C. product was ground to a powder and was stirred PHILIP S. WINNEK. with dilute ammonium hydroxide. The insoluble H. ELDRIDGE FAITH. portion was filtered off and the filtrate was acidifled with 10% hydrochloric acid. Th precipitate No references cited. 

